Coenzyme Q10 is of critical importance to mitochondrial function and its deficiency is associated with impaired ATP synthesis, apoptosis, and immune function. Its decease in tissue levels with age is associated with mitochondrial dysfunction and aging. There have been no major epidemiologic studies exploring the relationship between Coenzyme Q10 and breast cancer incidence and all cause mortality. Indeed, prospective studies relating this major endogenous lipid-phase anti-oxidant and key element of the electron transport chain to any type of cancer are nonexistent. Intriguing small clinical studies have suggested a possible beneficial effect of Coenzyme Q10, however supportive epidemiologic data is not available. There is compelling evidence that Coenzyme Q10 may play an important general role in the development and progression of many tumor types and preliminary evidence for an association with prostate cancer incidence and all- cause mortality in men is presented. It is proposed to utilize stored extracts from 2,193 women (731 incident cases of breast cancer and 1,462 matched controls) from two large prospective cohorts to determine the association of plasma coenzyme Q10 with breast cancer risk and all-cause mortality. In addition we observe intriguing relationships between Coenzyme Q10 and plasma levels of alpha and gamma-tocopherols, as well as C-Reactive Protein that may have a significant impact on the interpretation of the role of these dietary lipid-phase antioxidants on cancer development and progression in general. Analysis of Coenzyme Q10 in tandem with the individual tocopherols should provide significant new insight into the possible role of these essential lipids in the etiology of breast cancer and aging, as well as the interpretation of the meaning of plasma levels of these molecules. We hypothesize that an optimal level of Coenzyme Q10 will be determined that is associated with reduced risk for breast cancer and all- cause mortality. The project will explore the relation between coenzyme Q10, alpha-tocopherol, and gamma-tocopherol with breast cancer incidence and all-cause mortality in women utilizing previously collected samples from 2,193 women. It will greatly benefit our understanding of the association of these essential lipids with breast cancer and help to elucidate the potential role of plasma coenzyme Q10 in human physiology. [unreadable] [unreadable] [unreadable]